CENTRAL NERVOUS SYSTEM (CNS) : TECHNOLOGIES AND GLOBAL MARKETS BIO074C March 2016 Jackson Highsmith Project Analyst ISBN: 1-62296-246-X BCC Research 49 Walnut Park, Building 2 Wellesley, MA 02481 USA 866-285-7215 (toll-free within the USA), or (+1) 781-489-7301 www.bccresearch.com information@bccresearch.com
TABLE OF CONTENTS CHAPTER 1 INTRODUCTION 2 STUDY GOALS AND OBJECTIVES 2 REASONS FOR DOING THE STUDY 2 SCOPE OF REPORT 2 INTENDED AUDIENCE 3 METHODOLOGY AND INFORMATION SOURCES 4 ANALYST'S CREDENTIALS 4 RELATED BCC RESEARCH REPORTS 5 BCC RESEARCH WEBSITE 5 DISCLAIMER 5 CHAPTER 2 SUMMARY 7 SUMMARY TABLE GLOBAL MARKET FOR CNS BY APPLICATION, SUMMARY FIGURE GLOBAL MARKET FOR CNS BY APPLICATION, 2013-2020 ($ MILLIONS) 7 7 CHAPTER 3 OVERVIEW 11 INTRODUCTION 11 TABLE 1 GLOBAL MARKET FORECAST FOR CNS BY AREA, THROUGH 2020 ($ MILLIONS) TABLE 2 GLOBAL MARKET FOR CNS BY AREA, THROUGH 2015 ($ MILLIONS) TABLE 3 IN DRUG DISCOVERY: CNS MARKET, THROUGH 2020 (%) FOR CANCER 14 TABLE 4 MARKET SHARE OF CNS SUBSEGMENTS, 2015 ($ MILLIONS/ %) 14 TABLE 5 PERCENTAGE OF PREDICTIVE FOR CANCER PATIENTS BY SEGMENT, 2010-2020 (%) TABLE 6 FREQUENCY OF APPROACH IN CLAIMS REVIEW BY PAYERS, 2013-2020 (%) 16 TABLE 7 RELATIVE IMPORTANCE OF REIMBURSEMENT DECISIONS OF TEST FACTORS, 2009-2015 (%) FOR NON-ONCOLOGY INDICATIONS 18 DISEASE-SPECIFIC AND COMPANION DIAGNOSTICS 19 CSF 21 PERIPHERAL 22 ULTRA-BLOCKBUSTER 24 TABLE 8 CNS 25 TABLE 9 INFORMATION TECHNOLOGY (IT) STRATEGIES 26 ON TARGET 26 TABLE 10 INITIAL DESIGNS AND CAPABILITIES 27 ADAPTING TO DATA 27 SAFETY/TOXICOLOGY 27 LIVER 28 MUSCLE 28 CARDIAC HYPERTROPHY 28 VASCULAR INJURY 29 12 13 13 15 16
DOSE SELECTION AND OPTIMIZATION 29 NEW EFFORT AIMED AT DOSE SELECTION 29 IMPROVED MEASUREMENT OF THERAPEUTIC EFFICACY 30 Developing a New Framework for Long-term Addiction Treatment 30 Approach #1: Standard Treatment Patient Outcome Assessment 31 Approach #2: Independent Outcome Assessment Focused on Patient Satisfaction Approach #3: Recovery-Oriented System Model and Healthcare 31 OUTCOME AND SURROGATE END POINTS 32 TABLE 11 SUMMARY OF IOM RECOMMENDATIONS FOR A FRAMEWORK FOR EFFECTIVE BIOMARKER EVALUATION TABLE 12 SUMMARY OF IOM RECOMMENDATIONS FOR A FRAMEWORK FOR EFFECTIVE BIOMARKER EVALUATION: SCIENTIFIC PROCESS HARMONIZATION TABLE 13 BENEFITS OF AS SURROGATE END POINTS 33 CHALLENGES TO TRAUMATIC BRAIN INJURY (TBI) BIOMARKER DEVELOPMENT TABLE 14 HOW MIGHT FACILITATE TBI THERAPY DEVELOPMENT 34 Immediate Action Items 34 EARLY STAGE CLINICAL TRIAL APPLICATIONS 35 SUMMARY OF BIOMARKER CHALLENGES AND OPPORTUNITIES 36 CHALLENGES 38 OPPORTUNITIES 39 PROTEIN BIOMARKER TECHNOLOGY PLATFORMS: HYPOTHESIS-DRIVEN VS HYPOTHESIS-FREE APPROACHES REQUIREMENTS FOR CLINICAL VALIDITY 41 BIOMARKER PROGRESS 42 ENVIRONMENTAL EXPOSURES, EFFECT MODIFIERS, OR RISK FACTORS 42 TABLE 15 CROSS-SECTIONAL INVESTIGATIONS 43 INTERMEDIATE 43 SCREENING, DIAGNOSTIC TESTS, AND PROGNOSIS 43 VARIABILITY 44 VALIDITY 44 PRODUCT SUMMARY AND MARKET 46 GENOMICS 46 TABLE 16 GLOBAL MARKETS FOR CNS THROUGH 2015 ($ MILLIONS) 46 Progress in Genomic Biomarker Development 47 Emerging Evidence 47 Democratizing Health Care 48 BIOMARKER ADOPTION BY THE PHARMACEUTICAL INDUSTRY 48 CANCER : ADOPTION IS DRIVING GROWTH 52 TABLE 17 CLINICAL PATIENT MONITORING FOR CNS, AS COMPARED TO OTHER DISEASES (%) CLINICAL TRIAL BENEFITS: COST AND RISK AVOIDANCE 54 PHASE II TRIALS 54 PHASE IIA BASKET DISCOVERY TRIALS 55 PHASE III TARGETED (ENRICHMENT) DESIGNS 56 PHASE III BIOMARKER STRATIFIED DESIGN 57 PHASE III ADAPTIVE THRESHOLD DESIGN 58 BIOMARKER MARKET FORECAST 59 31 32 33 34 41 53
TABLE 18 GLOBAL MARKET FORECAST FOR CNS BY TECHNOLOGY, 59 CHAPTER 4 REGULATORY DYNAMICS, INTELLECTUAL PROPERTY, ETHICAL CONSIDERATIONS INTRODUCTION 61 BIOMARKER LABORATORY REGULATORY SUMMARY 61 DEFINITION OF AN IVD COMPANION DIAGNOSTIC 62 Labeling 64 TABLE 19 PHARMACOGENOMIC IN DRUG LABELING 65 REGULATORY PROCESSES FOR NEW TECHNOLOGIES 80 ENSURING SAFETY AND EFFECTIVENESS OF HEALTH TECHNOLOGIES 80 SAFE FOR WIDESPREAD USE? 80 REVIEW IN THE DEVELOPING WORLD 80 ASSAY DEVELOPMENT AND VALIDATION IN DRUG DIAGNOSTIC CO-DEVELOPMENT KEY DRAFT GUIDANCE POINTS FOR IVD COMPANION DIAGNOSTIC DEVICES: 82 SOME RELEVANT FDA GUIDANCE DOCUMENTS FOR CO-DEVELOPMENT 83 PIPELINE FOR BIOMARKER DEVELOPMENT 86 CLINICAL CONCEPTIONS ON THE STUDY DESIGN 87 TECHNICAL CONSIDERATIONS REGARDING THE ANALYTICAL SET UP FOR BIOMARKER DEVELOPMENT DISCOVERY OF 88 GEL-BASED PROTEOMICS PLATFORMS FOR BIOMARKER DISCOVERY 89 SHOTGUN PROTEOMICS 90 CE-MS 91 STATISTICAL DATA MINING FOR PROTEOMIC BIOMARKER DISCOVERY 91 VERIFICATION OF 92 PROTEIN BINDING ASSAYS 92 MASS SPECTROMETRIC QUANTITATIVE APPROACHES 93 PRE-TREATMENT STRATEGIES 93 DATA MINING AND STATISTICAL ANALYSIS 94 BIOINFORMATICS PLATFORMS IN CLINICAL PROTEOMICS 94 APPLICATIONS OF SYSTEMS BIOLOGY---DISEASE DIAGNOSIS AND TREATMENT VALIDATION OF BIOMARKER CANDIDATES 95 APPLICATION OF PROTEOMICS APPROACHES IN BCA BIOMARKER DISCOVERY Analytical Validation of a Companion Diagnostic 97 COMPANION DIAGNOSTIC VALIDATION 98 CLINICAL VALIDATION 99 OVERVIEW OF ESSENTIAL TYPES OF 100 TABLE 20 BIOMARKER CATEGORIES AND TYPES 101 OVERVIEW OF ALREADY APPROVED CDX ON THE MARKETS 102 KEY POINTS TO BE ADDRESSED 102 CONSIDERATIONS BEFORE INITIATING THE BIOMARKER DISCOVERY PHASE 103 CONSIDERATIONS ON THE SELECTION AND RANDOMIZATION OF PATIENTS FOR BIOMARKER STUDIES: LOOKING FOR THE 'IDEAL' PATIENTS THE CURRENT STATE OF BIOMARKER DISCOVERY 104 61 81 87 94 97 103
PITFALLS AND LIMITATIONS 104 SELECTION OF PATIENTS AND CONTROLS 105 ROLE OF THE FOOD & DRUG ADMINISTRATION 105 FDA GUIDELINES FOR BIOMARKER APPLICATIONS 105 TABLE 21 BIOMARKER QUALIFICATION PROGRAM 107 EUROPEAN MEDICINES AGENCY 108 REGULATORY IMPACT ON DRUG SAFETY 108 INTELLECTUAL PROPERTY AND COMPETITIVE POSITIONING 109 Approved Patent Analysis 109 TABLE 22 ANNUAL NUMBER OF PATENTS FILED AND APPROVED WITH BIOMARKER CLAIMS IN THE U.S., EUROPE, AND JAPAN, THROUGH 2015 (NUMBER/%) COMPETITIVE LANDSCAPE 109 LATE STAGE CLINICAL TRIALS: COMPETITIVE POSITIONING 110 TABLE 23 GLOBAL MARKET FOR TOTAL CLINICAL STAGE BY SERVICES AND PRODUCTS, TABLE 24 SUMMARY OF RECENT AGREEMENTS IN BIOMARKER DELIVERY, 2007-2014 TABLE 25 REPRESENTATIVE LIST OF APPROVED BIOMARKER PATENTS IN THE U.S., EUROPE, AND JAPAN 109 110 111 114 CHAPTER 5 APPLICATIONS OF CNS 119 OVERVIEW 119 TABLE 26 GLOBAL MARKET FOR CLINICAL STAGE BY THERAPEUTIC AREA, CENTRAL NERVOUS SYSTEM 122 TABLE 27 REPRESENTATIVE IN CLINICAL USE: CNS DISEASE 122 CLINICAL : THERAPEUTIC DISEASE MARKET FORECAST 123 TABLE 28 GLOBAL MARKET FORECAST FOR CLINICAL STAGE, TABLE 29 GLOBAL MARKET FORECAST FOR CNS IN LATE STAGE CLINICAL USE, 121 123 123 CHAPTER 6 ACTIVELY GUIDING DRUG DEVELOPMENT 125 AN OVERVIEW 125 TABLE 30 RELEVANT CORPORATE ALLIANCE BETWEEN A REFERENCE LAB AND A DRUG DEVELOPMENT COMPANY 126 CHAPTER 7 COMPANY ANALYSIS 128 ABBOTT LABORATORIES INC. 128 COMPANY OVERVIEW 128 PRODUCTS AND SERVICES 128 TABLE 31 ABBOTT'S REPRESENTATIVE CLINICAL TRIALS INVOLVING 128 COMPANY STRATEGY 129 AFFYMETRIX INC. 129 COMPANY OVERVIEW 129 PRODUCTS AND SERVICES 130 TABLE 32 AFFYMETRIX'S REPRESENTATIVE CLINICAL TRIALS INVOLVING COMPANY STRATEGY 130 130
ASTELLAS PHARMA INC. 131 COMPANY OVERVIEW 131 PRODUCTS AND SERVICES 131 TABLE 33 ASTELLAS' REPRESENTATIVE CLINICAL TRIALS INVOLVING 132 COMPANY STRATEGY 132 ASTRAZENECA LTD. 132 COMPANY OVERVIEW 132 PRODUCTS AND SERVICES 133 TABLE 34 ASTRAZENECA'S REPRESENTATIVE CLINICAL TRIALS INVOLVING COMPANY STRATEGY 133 BANYAN INC. 134 COMPANY OVERVIEW 134 PRODUCTS AND SERVICES 134 TABLE 35 BANYAN'S REPRESENTATIVE CLINICAL TRIALS INVOLVING 134 COMPANY STRATEGY 135 BAYER SCHERING PHARMA AG 135 COMPANY OVERVIEW 135 PRODUCTS AND SERVICES 135 TABLE 36 BAYER SCHERING'S REPRESENTATIVE CLINICAL TRIALS INVOLVING COMPANY STRATEGY 136 BG MEDICINE INC. 138 COMPANY OVERVIEW 138 PRODUCTS AND SERVICES 138 TABLE 37 BIOPHYSICAL REPRESENTATIVE CLINICAL TRIALS INVOLVING COMPANY STRATEGY 138 BIOPHYSICAL CORP. 139 COMPANY OVERVIEW 139 PRODUCTS AND SERVICES 139 COMPANY STRATEGY 139 BIOSYSTEMS INTERNATIONAL INC. 140 COMPANY OVERVIEW 140 PRODUCTS AND SERVICES 140 COMPANY STRATEGY 140 BOEHRINGER INGELHEIM GMBH 141 COMPANY OVERVIEW 141 PRODUCTS AND SERVICES 141 TABLE 38 BMS REPRESENTATIVE CLINICAL TRIALS INVOLVING 141 COMPANY STRATEGY 142 BRISTOL-MYERS SQUIBB CO. 142 COMPANY OVERVIEW 142 PRODUCTS AND SERVICES 142 TABLE 39 BMS REPRESENTATIVE CLINICAL TRIALS INVOLVING 143 COMPANY STRATEGY 143 CAPRION PROTEOMICS INC. 144 COMPANY OVERVIEW 144 133 136 138
PRODUCTS AND SERVICES 144 COMPANY STRATEGY 144 Infectious Diseases 144 Diabetes and Metabolic Disease 145 Oncology 145 DAIICHI SANKYO COMPANY LTD. 145 COMPANY OVERVIEW 145 PRODUCTS AND SERVICES 145 TABLE 40 DAIICHI SANKYO'S REPRESENTATIVE CLINICAL TRIALS INVOLVING COMPANY STRATEGY 146 EISAI CO. LTD. 147 COMPANY OVERVIEW 147 PRODUCTS AND SERVICES 147 TABLE 41 EISAI'S REPRESENTATIVE CLINICAL TRIALS INVOLVING 147 COMPANY STRATEGY 148 ELI LILLY AND COMPANY 148 COMPANY OVERVIEW 148 PRODUCT AND SERVICES 148 TABLE 42 ELI LILLY'S REPRESENTATIVE CLINICAL TRIALS INVOLVING 149 COMPANY STRATEGY 149 EPIGENOMICS AG 149 COMPANY OVERVIEW 150 PRODUCTS AND SERVICES 150 TABLE 43 EPIGENOMICS' REPRESENTATIVE CLINICAL TRIALS INVOLVING COMPANY STRATEGY 150 GENEDATA AG 151 COMPANY OVERVIEW 151 PRODUCTS AND SERVICES 151 TABLE 44 GENEDATA'S REPRESENTATIVE CLINICAL TRIALS INVOLVING COMPANY STRATEGY 152 GENENEWS LTD 152 COMPANY OVERVIEW 152 PRODUCTS AND SERVICES 152 COMPANY STRATEGY 152 GLAXOSMITHKLINE 153 COMPANY OVERVIEW 153 PRODUCTS AND SERVICES 153 TABLE 45 GSK'S REPRESENTATIVE CLINICAL TRIALS INVOLVING 153 COMPANY STRATEGY 154 JOHNSON & JOHNSON LTD. 154 COMPANY OVERVIEW 154 PRODUCTS AND SERVICES 155 TABLE 46 JOHNSON & JOHNSON'S REPRESENTATIVE CLINICAL TRIALS INVOLVING COMPANY STRATEGY 155 146 150 151 155
MERCK & CO. 156 COMPANY OVERVIEW 156 PRODUCTS AND SERVICES 156 TABLE 47 MERCK'S REPRESENTATIVE CLINICAL TRIALS INVOLVING 156 COMPANY STRATEGY 157 NOVARTIS AG 157 COMPANY OVERVIEW 157 PRODUCTS AND SERVICES 158 TABLE 48 NOVARTIS' REPRESENTATIVE CLINICAL TRIALS INVOLVING 158 COMPANY STRATEGY 158 PFIZER INC. 159 COMPANY OVERVIEW 159 PRODUCTS AND SERVICES 159 TABLE 49 PFIZER'S REPRESENTATIVE CLINICAL TRIALS INVOLVING 159 COMPANY STRATEGY 160 ROCHE LTD 160 COMPANY OVERVIEW 160 PRODUCTS AND SERVICES 161 TABLE 50 ROCHE'S REPRESENTATIVE CLINICAL TRIALS INVOLVING 161 COMPANY STRATEGY 161 SANOFI 162 COMPANY OVERVIEW 162 PRODUCTS AND SERVICES 162 TABLE 51 SANOFI'S REPRESENTATIVE CLINICAL TRIALS INVOLVING 163 COMPANY STRATEGY 163 TAKEDA PHARMACEUTICALS LTD. 164 COMPANY OVERVIEW 164 PRODUCTS AND SERVICES 164 TABLE 52 TAKEDA'S PHARMACEUTICALS REPRESENTATIVE CLINICAL TRIALS INVOLVING COMPANY STRATEGY 165 TEVA PHARMACEUTICAL INDUSTRIES LTD. 165 COMPANY OVERVIEW 165 PRODUCTS AND SERVICES 166 TABLE 53 TEVA'S PHARMACEUTICAL REPRESNTATIVE CLINICAL TRIALS INVOLVING COMPANY STRATEGY 167 164 166
LIST OF TABLES TABLE HEADING SUMMARY TABLE GLOBAL MARKET FOR CNS BY APPLICATION, TABLE 1 GLOBAL MARKET FORECAST FOR CNS BY AREA, THROUGH 2020 ($ MILLIONS) TABLE 2 GLOBAL MARKET FOR CNS BY AREA, THROUGH 2015 ($ MILLIONS) TABLE 3 IN DRUG DISCOVERY: CNS MARKET, THROUGH 2020 (%) TABLE 4 MARKET SHARE OF CNS SUBSEGMENTS, 2015 ($ MILLIONS/ %) 14 TABLE 5 PERCENTAGE OF PREDICTIVE FOR CANCER PATIENTS BY SEGMENT, 2010-2020 (%) TABLE 6 FREQUENCY OF APPROACH IN CLAIMS REVIEW BY PAYERS, 2013-2020 (%) 16 TABLE 7 RELATIVE IMPORTANCE OF REIMBURSEMENT DECISIONS OF TEST FACTORS, 2009-2015 (%) TABLE 8 CNS 25 TABLE 9 INFORMATION TECHNOLOGY (IT) STRATEGIES 26 TABLE 10 INITIAL DESIGNS AND CAPABILITIES 27 TABLE 11 SUMMARY OF IOM RECOMMENDATIONS FOR A FRAMEWORK FOR EFFECTIVE BIOMARKER EVALUATION TABLE 12 SUMMARY OF IOM RECOMMENDATIONS FOR A FRAMEWORK FOR EFFECTIVE BIOMARKER EVALUATION: SCIENTIFIC PROCESS HARMONIZATION TABLE 13 BENEFITS OF AS SURROGATE END POINTS 33 TABLE 14 HOW MIGHT FACILITATE TBI THERAPY DEVELOPMENT 34 TABLE 15 CROSS-SECTIONAL INVESTIGATIONS 43 TABLE 16 GLOBAL MARKETS FOR CNS THROUGH 2015 ($ MILLIONS) 46 TABLE 17 CLINICAL PATIENT MONITORING FOR CNS, AS COMPARED TO OTHER DISEASES (%) TABLE 18 GLOBAL MARKET FORECAST FOR CNS BY TECHNOLOGY, TABLE 19 PHARMACOGENOMIC IN DRUG LABELING 65 TABLE 20 BIOMARKER CATEGORIES AND TYPES 101 TABLE 21 BIOMARKER QUALIFICATION PROGRAM 107 TABLE 22 ANNUAL NUMBER OF PATENTS FILED AND APPROVED WITH BIOMARKER CLAIMS IN THE U.S., EUROPE, AND JAPAN, THROUGH 2015 (NUMBER/%) TABLE 23 GLOBAL MARKET FOR TOTAL CLINICAL STAGE BY SERVICES AND PRODUCTS, TABLE 24 SUMMARY OF RECENT AGREEMENTS IN BIOMARKER DELIVERY, 2007-2014 111 TABLE 25 REPRESENTATIVE LIST OF APPROVED BIOMARKER PATENTS IN THE U.S., EUROPE, AND JAPAN TABLE 26 GLOBAL MARKET FOR CLINICAL STAGE BY THERAPEUTIC AREA, TABLE 27 REPRESENTATIVE IN CLINICAL USE: CNS DISEASE 122 TABLE 28 GLOBAL MARKET FORECAST FOR CLINICAL STAGE, TABLE 29 GLOBAL MARKET FORECAST FOR CNS IN LATE STAGE CLINICAL USE, TABLE 30 RELEVANT CORPORATE ALLIANCE BETWEEN A REFERENCE LAB AND A DRUG DEVELOPMENT COMPANY TABLE 31 ABBOTT'S REPRESENTATIVE CLINICAL TRIALS INVOLVING 128 7 12 13 13 15 16 32 33 53 59 109 110 114 121 123 123 126
TABLE HEADING TABLE 32 AFFYMETRIX'S REPRESENTATIVE CLINICAL TRIALS INVOLVING TABLE 33 ASTELLAS' REPRESENTATIVE CLINICAL TRIALS INVOLVING 132 TABLE 34 ASTRAZENECA'S REPRESENTATIVE CLINICAL TRIALS INVOLVING TABLE 35 BANYAN'S REPRESENTATIVE CLINICAL TRIALS INVOLVING 134 TABLE 36 BAYER SCHERING'S REPRESENTATIVE CLINICAL TRIALS INVOLVING TABLE 37 BIOPHYSICAL REPRESENTATIVE CLINICAL TRIALS INVOLVING 138 TABLE 38 BMS REPRESENTATIVE CLINICAL TRIALS INVOLVING 141 TABLE 39 BMS REPRESENTATIVE CLINICAL TRIALS INVOLVING 143 TABLE 40 DAIICHI SANKYO'S REPRESENTATIVE CLINICAL TRIALS INVOLVING TABLE 41 EISAI'S REPRESENTATIVE CLINICAL TRIALS INVOLVING 147 TABLE 42 ELI LILLY'S REPRESENTATIVE CLINICAL TRIALS INVOLVING 149 TABLE 43 EPIGENOMICS' REPRESENTATIVE CLINICAL TRIALS INVOLVING TABLE 44 GENEDATA'S REPRESENTATIVE CLINICAL TRIALS INVOLVING 151 TABLE 45 GSK'S REPRESENTATIVE CLINICAL TRIALS INVOLVING 153 TABLE 46 JOHNSON & JOHNSON'S REPRESENTATIVE CLINICAL TRIALS INVOLVING TABLE 47 MERCK'S REPRESENTATIVE CLINICAL TRIALS INVOLVING 156 TABLE 48 NOVARTIS' REPRESENTATIVE CLINICAL TRIALS INVOLVING 158 TABLE 49 PFIZER'S REPRESENTATIVE CLINICAL TRIALS INVOLVING 159 TABLE 50 ROCHE'S REPRESENTATIVE CLINICAL TRIALS INVOLVING 161 TABLE 51 SANOFI'S REPRESENTATIVE CLINICAL TRIALS INVOLVING 163 TABLE 52 TAKEDA'S PHARMACEUTICALS REPRESENTATIVE CLINICAL TRIALS INVOLVING TABLE 53 TEVA'S PHARMACEUTICAL REPRESNTATIVE CLINICAL TRIALS INVOLVING 130 133 136 146 150 155 164 166
LIST OF FIGURES FIGURE TITLE SUMMARY FIGURE GLOBAL MARKET FOR CNS BY APPLICATION, 2013-2020 ($ MILLIONS) 7